The overall goal of this proposal is to determine if plasminogen activator secreted by organ cultures of human mammary tumors can be used as an indicator of hormonal responses of these tumors in vivo. The profile of responses to hormones of tumor growth in vivo and of tumor plasminogen activator production in vitro shows numerous correlations, suggesting that these two parameters may be coordinately regulated. Our studies on a large series of rodent mammary tumors induced by chemical carcinogens or virus have indicated that PA production in malignant tumors is part of a biosynthetic program induced by hormones which stimulate growth in vivo. The objective of this study is to test if such correlation exists in human breast cancer and if so, whether it can be utilized for designing specific hormonal therapy for individual patients with breast cancer. We plan to test approximately 300 breast cancers over a period of 3 years. These will be obtained from mastectomies or tumor biopsies through the Tumor Procurement Center at MSKCC. The estrogen and progesterone receptor status of these tumor as well as information concerning other tumor characteristics and response to treatment will be made available to us. The main hormones to be used in this study will be: 17Beta-estradiol, progesterone, prolactin, hydrocortisone and androgens; these will be added to organ cultures individually and in combination of 2 and 3. Additional hormones and several other compounds such as tamoxifen and retinoic acid will also be tested. We will also test the effect of a novel pituitary factor which we found to be highly active in rodent mammary tumors. These results will be compared to the hormone receptor status of these tumors and when possible with the response to hormonal therapy.